We Need to Talk About Notch:Notch Dysregulation as an Epiphenomenon in Inflammatory Skin Disease

Abstract

The Notch signaling pathway is a highly evolutionarily conserved signaling pathway comprised of four type 1 transmembrane receptors. Canonical Notch signaling is stimulated by Jagged and Delta ligands resulting in translocation of the Notch Intracellular domain (ICD) to the nucleus resulting in activation of transcription factor CSL. Increased Notch activity is associated with epidermal keratinocyte maturation, proliferation and innate immune activation through maturation of dendritic cells, T cells and macrophages.

This article is protected by copyright. All rights reserved.

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IL‐36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis

Abstract

Psoriasis vulgaris (PV) results from activation of IL‐23/Th17 immune pathway and is further amplified by cytokines/chemokines from skin cells. Among skin derived pro‐inflammatory cytokines, IL‐36 family members are highly upregulated in PV patients and play a critical role in general pustular psoriasis. However, there is limited data showing crosstalk between the IL‐23 and IL‐36 pathways in PV. Herein, potential attenuation of skin inflammation in the IL‐23‐induced mouse model of psoriasiform dermatitis by functional inhibition of IL‐36 receptor (IL‐36R) was interrogated. Anti‐mouse IL‐36R monoclonal antibodies (mAbs) were generated and validated in vitro by inhibiting IL‐36α induced secretion of CXCL1 from NIH 3T3 cells. Antibody target engagement was demonstrated by inhibition of CXCL1 production in a novel acute model of IL‐36α systemic injection in mice. In addition, anti‐IL‐36R mAbs inhibited tissue inflammation and inflammatory gene expression in an IL‐36α ear injection model of psoriasiform dermatitis demonstrating engagement of the target in the ear skin. To elucidate the possible role of IL‐36 signaling in IL‐23/Th17 pathway, the ability of anti‐IL‐36R mAbs to inhibit skin inflammation in an IL‐23 ear injection model was assessed. Inhibiting the IL‐36 pathway resulted in significant attenuation of skin thickening and psoriasis‐relevant gene expression. Taken together, this data suggests a role for IL‐36 signaling in the IL‐23/Th17 signaling axis in PV.

This article is protected by copyright. All rights reserved.

https://ift.tt/2DA2jWG

We Need to Talk About Notch:Notch Dysregulation as an Epiphenomenon in Inflammatory Skin Disease

Abstract

The Notch signaling pathway is a highly evolutionarily conserved signaling pathway comprised of four type 1 transmembrane receptors. Canonical Notch signaling is stimulated by Jagged and Delta ligands resulting in translocation of the Notch Intracellular domain (ICD) to the nucleus resulting in activation of transcription factor CSL. Increased Notch activity is associated with epidermal keratinocyte maturation, proliferation and innate immune activation through maturation of dendritic cells, T cells and macrophages.

This article is protected by copyright. All rights reserved.

https://ift.tt/2PYDdXC

Diagnostik beim nichtkleinzelligen Lungenkarzinom

Zusammenfassung

Grundlage für die Behandlung des nichtkleinzelligen Lungenkarzinoms sind eingehende Kenntnisse der zugrunde liegenden Krankheitscharakteristikamerkmale und der verschiedenen Therapieoptionen. Die Ergebnisse der Diagnostik sollten in einer interdisziplinären Tumorkonferenz eingeordnet werden. Die präzise Histologie und die genaue TNM-Klassifikation sind prognoserelevant und führen zu einer individuellen und optimalen Therapie. Der vorliegende Artikel wurde basierend auf nationalen und internationalen Leitlinien sowie auf einer selektiven PubMed-Suche erstellt.

https://ift.tt/2z86ghs

Effect of lights with various wavelengths on bleaching by 30% hydrogen peroxide

Abstract

The objective of this study was to evaluate the bleaching effect of light sources with various wavelengths using 30% hydrogen peroxide (HP) in vitro. The hematoporphyrin-stained paper was bleached with HP and irradiated for 10 min using LED light sources with 265, 310, 365, 405, or 450 nm respectively. In control group, HP was applied for 10 min without light irradiation. The bleaching procedure was repeated two times. The L*a*b* values of the samples before bleaching and after each bleaching step were measured using a colorimeter. Color changes of specimens were then calculated and statistically analyzed. There was an interaction between light sources and time of irradiation in the color change (p < 0.05). Time and light sources significantly affected ΔE and ΔL (p < 0.05). The light source of 256 nm showed the highest bleaching effect over time followed by that of 310 nm, which were statistically different from other groups (p < 0.001). The 365 nm, 450 nm groups, and control group showed low bleaching effect visually with no significant differences in ΔE and ΔL (p > 0.05). It was concluded that the wavelengths of the light sources affected the bleaching by HP. The 310-nm light can be a potential source for bleaching.

https://ift.tt/2qIFY0W

Determination of biochemical oxygen demand and dissolved oxygen for semi-arid river environment: application of soft computing models

Abstract

Surface and ground water resources are highly sensitive aquatic systems to contaminants due to their accessibility to multiple-point and non-point sources of pollutions. Determination of water quality variables using mathematical models instead of laboratory experiments can have venerable significance in term of the environmental prospective. In this research, application of a new developed hybrid response surface method (HRSM) which is a modified model of the existing response surface model (RSM) is proposed for the first time to predict biochemical oxygen demand (BOD) and dissolved oxygen (DO) in Euphrates River, Iraq. The model was constructed using various physical and chemical variables including water temperature (T), turbidity, power of hydrogen (pH), electrical conductivity (EC), alkalinity, calcium (Ca), chemical oxygen demand (COD), sulfate (SO₄), total dissolved solids (TDS), and total suspended solids (TSS) as input attributes. The monthly water quality sampling data for the period 2004–2013 was considered for structuring the input-output pattern required for the development of the models. An advance analysis was conducted to comprehend the correlation between the predictors and predictand. The prediction performances of HRSM were compared with that of support vector regression (SVR) model which is one of the most predominate applied machine learning approaches of the state-of-the-art for water quality prediction. The results indicated a very optimistic modeling accuracy of the proposed HRSM model to predict BOD and DO. Furthermore, the results showed a robust alternative mathematical model for determining water quality particularly in a data scarce region like Iraq.

https://ift.tt/2PXuuEK

The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes

Abstract

Succinate dehydrogenase (SDH) is an enzyme complex, composed of four protein subunits, that plays a role in both the citric acid cycle and the electron transport chain. The genes for SDHA, SDHB, SDHC, and SDHD are located in the nuclear DNA, and mutations in these genes have initially been described in paragangliomas (PGL) and pheochromocytomas (PCC), which are relatively rare tumors derived from the autonomic nervous system and the adrenal medulla, respectively. Patients with SDH mutations, that are almost exclusively in the germline, are frequently affected by multiple PGL and/or PCC. In addition, other tumors have been associated with SDH mutations as well, including gastrointestinal stromal tumors, SDH-deficient renal cell carcinoma, and pituitary adenomas. Immunohistochemistry for SDHB and SDHA has been shown to be a valuable additional tool in the histopathological analysis of these tumors, and can be considered as a surrogate marker for molecular analysis. In addition, SDHB immunohistochemistry is relevant in the decision-making whether a genetic sequence variant represents a pathogenic mutation or not. In this review, we highlight the current knowledge of the physiologic and pathologic role of the SDH enzyme complex and its involvement in endocrine and non-endocrine tumors, with an emphasis on the applicability of immunohistochemistry.

https://ift.tt/2Deq3yO

Improvement in Patient-Reported Outcomes (Dermatology Life Quality Index and the Psoriasis Symptoms and Signs Diary) with Guselkumab in Moderate-to-Severe Plaque Psoriasis: Results from the Phase III VOYAGE 1 and VOYAGE 2 Studies

Abstract

Background

Health-related quality of life (HRQoL) may be markedly impaired in patients with moderate-to-severe psoriasis.

Objectives

Our objectives were to compare improvements in Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) scores between patients receiving guselkumab compared with placebo or adalimumab and to correlate these improvements with skin clearance.

Methods

Pooled phase III VOYAGE 1 and VOYAGE 2 data were evaluated through week 24. At baseline, patients were randomized to guselkumab 100 mg, placebo, or adalimumab 40 mg. At week 16, patients receiving placebo switched to guselkumab. Assessment measures included DLQI percent change from baseline, DLQI 0/1, DLQI minimal clinically important difference (MCID), individual domain scores, PSSD symptoms and signs score = 0, DLQI association with PSSD, Investigator's Global Assessment (IGA), and Psoriasis Area and Severity Index (PASI).

Results

Significantly greater improvements from baseline DLQI were observed with guselkumab versus placebo (weeks 8 and 16) and versus adalimumab (week 24; p < 0.001). The proportion of patients achieving DLQI 0/1 ("no impact") at week 24 was higher with guselkumab than with adalimumab (58.9 vs. 40.2%; p < 0.001), and more patients attained a ≥ 4-point reduction in DLQI (MCID) at this timepoint (p < 0.001). Changes in individual DLQI domains were significantly greater for patients receiving guselkumab than for those receiving adalimumab, and among patients with individual baseline domain scores = 3 or 6 (severest impact), more guselkumab recipients than those receiving adalimumab achieved a score = 0 across all domains at week 24. DLQI 0/1 scores were associated with a PSSD symptom or sign score = 0 (no impact) and greater improvement of PASI and IGA (week 24).

Conclusions

Pooled VOYAGE 1/VOYAGE 2 data demonstrated that guselkumab was superior to adalimumab in improving HRQoL, which was associated with greater skin clearance.

Clinical Trial Registration

NCT02207231 and NCT02207244.

https://ift.tt/2FhCSuS

How Kentucky bluegrass tolerate stress caused by sodium chloride used for road de-icing?

Abstract

Salts used in road de-icing during winter season inhibit the growth and development of lawn grass species. The mechanism of plant tolerance/sensitivity to such treatments is still not clear. Moreover, there is a lack of fast and non-invasive tool to detect the effect of these salts on plants growth. This study was designed to understand the tolerance mechanism of Kentucky bluegrass plants on salinity, based on some biometric and physiological parameters. In this experiment, we simulated the urban conditions where salts are used intensively for roads de-icing. Germination capacity was evaluated at five salt solutions of NaCl (0, 50, 100, 150 and 200 mM), and physiological parameters were measured during the tillering phase at salinity levels of 0, 150 and 300 mM of NaCl. Seeds of Kentucky bluegrass did not germinate under salinity. During tillering phase, salinity affected length, area and dry mass of roots as well as the relative water content of plants, negatively. Moreover, it influenced the maximum chlorophyll fluorescence yield, quantum yield of photosystem II and electron transport rate at early period of stress. This allows us to recommend these parameters for early detection of soil salinity effects on Kentucky bluegrass plants. It seems to be that the tolerance of this plant towards salinity is based on retaining water content in leaves that allow more efficient functioning of photosynthetic apparatus.

https://ift.tt/2AYVdsw

Adsorption of gallic acid on nanoclay modified with poly(diallyldimethylammonium chloride)

Abstract

In this work, particles of nanoclay modified with poly(diallyldimethylammonium), PDDA, namely PDDA/PGV, were obtained and characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), surface area measurement (BET surface area), measurement of zero charge point (pH_PCZ), and scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS). The PDDA/PGV particles were applied as adsorbent for the removal of gallic acid (GA) from aqueous solution. The effect of various parameters, such as solution pH, contact time, adsorbent mass, and temperature, was studied. The maximum adsorption capacity of PDDA/PGV (238.45 mg g⁻¹) was observed at pH 4 and 15 °C. The study of adsorption kinetics and isotherms revealed that the adsorption process was better fitted by pseudo-first order and Freundlich model, respectively. The obtained thermodynamic parameters indicate that the adsorption of GA is spontaneous and enthalpy-driven.

https://ift.tt/2JXwUOq

Syringocystadenoma papilliferum of the cervix presenting as vulvar growth in an adolescent girl

Summary

Syringocystadenoma papilliferum (SCP) is a rare, benign, adnexal tumour of apocrine or eccrine differentiation. It is commonly located on head and neck region. We report the case of an 18‐year‐old woman who presented with a vulvar lobulated growth that was found to arise from the posterior lip of cervix. Histopathological examination revealed the diagnosis of SCP. To our knowledge, SCP arising from the cervix has never been reported previously in the literature, thus we believe this to be the first case of SCP arising from the posterior lip of the cervix.

https://ift.tt/2JXUURi

Syringocystadenoma papilliferum of the cervix presenting as vulvar growth in an adolescent girl

Summary

Syringocystadenoma papilliferum (SCP) is a rare, benign, adnexal tumour of apocrine or eccrine differentiation. It is commonly located on head and neck region. We report the case of an 18‐year‐old woman who presented with a vulvar lobulated growth that was found to arise from the posterior lip of cervix. Histopathological examination revealed the diagnosis of SCP. To our knowledge, SCP arising from the cervix has never been reported previously in the literature, thus we believe this to be the first case of SCP arising from the posterior lip of the cervix.

https://ift.tt/2JXUURi

Evaluation of the efficacy of microneedle fractional radiofrequency in Turkish patients with atrophic facial acne scars

Summary

Background

Scarring is an undesirable and severe complication of acne resulting in loss of self‐esteem in young people. Although microneedle fractional radiofrequency (MFR) system has emerged as a good option to treat acne scars in recent years, it was examined in a few studies which were commonly from Asian countries.

Aims

We sought to evaluate the efficacy of MFR in Turkish patients with facial acne scars.

Methods

Nine patients with atrophic facial acne scars treated with MFR device were included in the study. The number of treatment sessions was varied from one to five (median three) with 4‐week intervals. Demographic and basal clinical features were recorded. Efficacy of the device was evaluated by the physicians' global assessment and patients' self‐assessment scales 4 weeks after the last treatment session.

Results

Of nine patients, two were male and seven were female (mean age, 31.33 years). Two patients had mild, four had moderate, and three had severe facial acne scars. Mean acne scar age was 13.22 ± 8.79 years. According to the predominant scar subtype, three patients had V‐shaped, three had U‐shaped, and three had M‐shaped atrophic acne scars. A clinical improvement of >25% has been reported in seven patients (77.7%) and eight patients (88.9%) by the physicians and patients, respectively. U‐shaped atrophic acne scars responded better to the treatment than the other types, as statistically nonsignificant. There were no severe side effects.

Conclusions

Microneedle fractional radiofrequency system showed a quite good efficacy and safety in the treatment of atrophic facial acne scars (Department of Dermato‐Cosmetology, Uludag University Medical School).

https://ift.tt/2qHbdct

Evaluation of the efficacy of microneedle fractional radiofrequency in Turkish patients with atrophic facial acne scars

Summary

Background

Scarring is an undesirable and severe complication of acne resulting in loss of self‐esteem in young people. Although microneedle fractional radiofrequency (MFR) system has emerged as a good option to treat acne scars in recent years, it was examined in a few studies which were commonly from Asian countries.

Aims

We sought to evaluate the efficacy of MFR in Turkish patients with facial acne scars.

Methods

Nine patients with atrophic facial acne scars treated with MFR device were included in the study. The number of treatment sessions was varied from one to five (median three) with 4‐week intervals. Demographic and basal clinical features were recorded. Efficacy of the device was evaluated by the physicians' global assessment and patients' self‐assessment scales 4 weeks after the last treatment session.

Results

Of nine patients, two were male and seven were female (mean age, 31.33 years). Two patients had mild, four had moderate, and three had severe facial acne scars. Mean acne scar age was 13.22 ± 8.79 years. According to the predominant scar subtype, three patients had V‐shaped, three had U‐shaped, and three had M‐shaped atrophic acne scars. A clinical improvement of >25% has been reported in seven patients (77.7%) and eight patients (88.9%) by the physicians and patients, respectively. U‐shaped atrophic acne scars responded better to the treatment than the other types, as statistically nonsignificant. There were no severe side effects.

Conclusions

Microneedle fractional radiofrequency system showed a quite good efficacy and safety in the treatment of atrophic facial acne scars (Department of Dermato‐Cosmetology, Uludag University Medical School).

https://ift.tt/2qHbdct

Response of secondary metabolites to Cu in the Cu-hyperaccumulator lichen Stereocaulon japonicum

Abstract

Lichen secondary metabolites are known to be associated with heavy metal uptake and tolerance in lichens. Understanding the relationship between their secondary metabolites and heavy metals in them is important for clarifying the mechanisms of their heavy metal accumulation and tolerance. To determine the relationships between the concentrations of secondary metabolites and Cu in the Cu-hyperaccumulator lichen Stereocaulon japonicum and to clarify its response to Cu, we collected Cu-contaminated and uncontaminated samples of the lichen and determined relative concentrations of secondary metabolites and concentrations of Cu, K, glucose, and sugar alcohols in them. We found significant negative correlations between the relative concentrations of secondary metabolites—atranorin and stictic acid—and the concentration of Cu. These negative correlations can be interpreted in one of two ways: (a) S. japonicum itself reduced the relative concentrations of secondary metabolites in response to the increase of Cu concentration or (b) its carbon and energy metabolism was damaged by Cu stress, resulting in the reduction of the relative concentrations of secondary metabolites. The analysis of K, glucose, and sugar alcohols showed no effect of Cu on these concentrations, which means that the carbon and energy metabolism was not damaged by Cu stress. Therefore, the negative correlations can be interpreted that S. japonicum itself reduced the relative concentrations of secondary metabolites with the increase of Cu concentration. These findings provide a deeper understanding of the response of secondary metabolites to Cu in the lichen.

https://ift.tt/2DijThg

Insomnia and mortality: a meta-analysis

The purpose of this review was to evaluate the strength of evidence for a relationship between risk of mortality and frequent and ongoing insomnia using a meta-analytic strategy.Seventeen studies, including a total of 36,938,981 individuals followed up for a mean of 11.6 years, reporting the investigation of the association between mortality and frequent (≥3 nights/week), ongoing (≥1 month) insomnia were identified.There was no difference in the odds of mortality for those individuals with symptoms of insomnia when compared to those without symptoms (OR= 1.06, 95%CI=0.61-1.84, p=.84).

https://ift.tt/2Fgkkeh

Craniofacial and Dental Manifestations of Melnick–Needles Syndrome: Literature Review and Orthodontic Management

The aim of this article was to present a characteristic clinical image of Melnick–Needles syndrome using an example of an 11.5-year-old female patient treated at the Facial Congenital Disorders Outpatient Clinic as well as to present the actual literature review of the surgical treatment. The patient was diagnosed with several characteristics typical for Melnick–Needles syndrome: single-sided hearing loss, malocclusion, and facial dysmorphism, among others. Due to malocclusion and facial dysmorphism, the patient with Melnick–Needles syndrome requires orthodontic treatment with surgical intervention. Mandibular distraction with fixed appliance treatment is a recommended treatment protocol.

https://ift.tt/2z3uxoQ

Cochlear Ossification in a Patient with Cogan’s Syndrome Undergoing Bilateral Cochlear Implantation

We present the case of a young female patient diagnosed with Cogan's syndrome after the rapid onset of profond hearing and vestibular loss with concomitant eye symptoms. After appropriate medical treatment, her hearing did not respond and she underwent bilateral simultaneous cochlear implantation with findings of extensive cochlear ossification in both ears. The case and outcome are described in the body of the paper.

https://ift.tt/2DBhGOA

A novel GNRHR gene mutation causing Congenital Hypogonadotropic Hypogonadism (CHH) in a Brazilian Kindred

Abstract

Congenital Hypogonadotropic Hypogonadism (CHH) is a challenging inherited endocrine disorder characterized by absent or incomplete pubertal development and infertility due to low action/secretion of the hypothalamic gonadotrophin‐releasing hormone (GnRH). Given a growing list of gene mutations accounting for CHH, application of massively parallel sequencing has become an excellent molecular diagnosis approach since it has enabled simultaneous evaluation of many genes. The study proposes the use of Whole Exome Sequencing (WES) to identify causative and modifying mutations based on a phenotype‐genotype CHH analysis by in‐house exome pipeline. Based on 44 known genes related to CHH in humans, we were able to identify a novel homozygous GNRHR p.Thr269Met mutant, which segregates with CHH kindred and was predicted to be deleterious by in silico analysis. A functional study measuring intracellular inositol phosphate (IP) when stimulated with GnRH on COS‐7 cells confirmed that the p.Thr269Met GnRHR mutant performed greatly diminished IP accumulation relative to the transfected wild‐type GnRHR. Additionally, the proband carries three heterozygous variants in CCDC141 and one homozygous in SEMA3A gene, but their effects in modifying the phenotype are uncertain. Since they do not segregate with reproductive phenotype in family members, we advocate they do not contribute to CHH oligogenicity. WES proved to be useful for CHH molecular diagnosis and reinforced its benefit for identifying heterogeneous genetic disorders. Our findings expand the GnRHR mutation spectrum and phenotype‐genotype correlation in CHH.

This article is protected by copyright. All rights reserved.

https://ift.tt/2RIzsCK

Dividing neutrophils in subsets, reveals a significant role for activated neutrophils in the development of airway hyperreactivity

Abstract

Background

Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality of neutrophils in the inflammatory process has recently changed and knowledge about subsets of neutrophils, as characterized by their expression of CD16 and CD62L, has surfaced. Their specific roles in asthma are still unknown.

Objective

To study the functional differences between subsets of neutrophils by characterising the impact of individual subsets on airway smooth muscle reactivity.

Methods

The direct effect of neutrophils on airway hyper‐responsiveness was assessed by co‐culturing different subsets of neutrophils (produced by LPS in vitro stimulation) with human isolated small airways or murine tracheae with subsequent evaluation of smooth muscle reactivity to bradykinin in myographs. Supernatants and tissue were saved for ELISA and immunohistochemistry.

Results

The CD16^highCD62L^dim neutrophils were found to enhance the response to bradykinin in both human isolated small airways and murine tracheae. No such effects were obtained for the other subsets. The response is due to an upregulation of bradykinin receptor 2 through release of TNFα from the neutrophil.

Conclusions & Clinical Relevance

The present study introduces a new concept regarding the role of neutrophils and defines a novel direct link between a specific activated neutrophil subset and airway smooth muscle, establishing neutrophils as important players in the development of asthmatic airway hyperactivity.

This article is protected by copyright. All rights reserved.

https://ift.tt/2RNmC69

Variability of blood eosinophils in patients in a clinic for severe asthma

Abstract

Background

Blood eosinophils are used to determine eligibility for agents targeting IL‐5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation.

Objective

To characterize variability and patterns of variability of blood eosinophil levels in a real‐world clinic for severe asthmatics.

Methods

Retrospective review of blood eosinophils measured over a 5‐year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analyzed.

Results

Patients treated in the Bellevue Hospital Asthma Clinic within a 3‐month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n= 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures.

Conclusion

In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability. These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention.

This article is protected by copyright. All rights reserved.

https://ift.tt/2DznsjI

Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea pigs

Abstract

Background

The pathogenesis and pathophysiology of eosinophilia‐related chronic cough such as non‐asthmatic eosinophilic bronchitis and cough variant asthma are still not clear.

Objective

This study is to examine the potential role of traffic‐related air pollution (TRAP) in eosinophilic inflammation and cough responses.

Methods

Non‐sensitized guinea pigs were exposed to TRAP in an urban traffic tunnel or kept in a filtered air environment for 7 or 14 days. Reflexive cough was measured using citric acid and allyl isothiocyanate (AITC) challenges, respectively. Spontaneous cough counting was determined using audio recording and a waveform analysis. Airway inflammation was evaluated using differential cells in bronchoalveolar lavage fluid (BALF) and lung histopathology. To further elucidate the relationship between airway inflammation and cough hypersensitivity, a subgroup of those exposed for 14 days received a dexamethasone treatment.

Results

Compared to reflexive cough count (mean (95% confidence interval) in 10 min) provoked by the AITC challenge for the unexposed animals (3.1 (1.7‐4.5)), those were increased significantly following both the 7‐day (12.0 (6.8‐17.2), p<0.01) and the 14‐day (12.0 (6.4‐17.6), p<0.01) TRAP exposure. The effect provoked by the citric acid challenge was more profound following the 14‐day exposure (26.0 (19.5‐32.5) vs. 3.8 (1.5‐6.0) for the control, p<0.001). TRAP exposures enhanced spontaneous cough events, caused a significant increase of eosinophils and neutrophils in BALF, and resulted in a dramatic eosinophilic infiltration in submucosal layer of trachea and bronchus, which can be inhibited significantly by dexamethasone treatment.

Conclusions & Clinical Relevance

TRAP exposures induced cough hypersensitivity and non‐allergic eosinophilic inflammation of airways in guinea pigs. This study highlights the potential mechanisms of eosinophilia‐related chronic cough that can be induced by traffic‐related air pollution.

This article is protected by copyright. All rights reserved.

https://ift.tt/2RNmuDH

Antihistamine‐resistant chronic spontaneous urticaria: 1‐year data from the AWARE study

Abstract

Background

Previous reports indicate that patients with chronic spontaneous urticaria (CSU) are undertreated and that physicians show poor adherence to guideline recommendations. Awareness of CSU has improved in recent years, but it remains unclear if this has improved the management of these patients in clinical practice.

Objective

To describe disease burden, quality of life (QoL), and treatment patterns of patients with H₁‐antihistamine‐refractory CSU in Germany.

Method

AWARE (A World‐wide Antihistamine‐Refractory chronic urticaria patient Evaluation) is a global prospective, non‐interventional study of chronic urticaria in the real‐world setting, supported by the manufacturer of omalizumab. Patients (18–75 years) were included who had H₁‐antihistamine‐refractory CSU for ≥2 months. Disease characteristics, pharmacological treatments, and QoL (dermatology life quality index [DLQI], chronic urticaria QoL questionnaire, and angioedema QoL questionnaire) are reported for patients enrolled in Germany.

Results

After 1 year in AWARE, CSU remained uncontrolled (urticaria control test [UCT] score <12) in 432 of 1032 (42.2%) patients. QoL impairment remained high after one year, with 28.2% of patients reporting that CSU had a moderate/very large/extremely large effect on the DLQI. Most patients did not receive guideline‐recommended treatments at the end of the one‐year observation period. Changes in treatments were most evident at the first patient visit, with an increase in patients receiving omalizumab vs. prior therapy from 8.5% to 21.4%, and a decrease in those receiving no treatment from 29.9% to 12.8%. These changes were associated with reduced hives, angioedema, UCT scores, and QoL scores at Month 3, but only modest improvements thereafter. Of 528 patients with uncontrolled CSU and who were eligible for treatment escalation, only 3% received up‐dosing of H₁‐antihistamines and only 5% were initiated on omalizumab during one year of treatment.

Conclusions & Clinical Relevance

This study highlights a significant discrepancy between recommendations for managing CSU in international guidelines, and in real‐world clinical practice in Germany.

This article is protected by copyright. All rights reserved.

https://ift.tt/2DABGBh

Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation

Publication date: Available online 10 November 2018

Source: Allergology International

Author(s): Takashi Ito, Koichi Hirose, Hiroshi Nakajima

Abstract

Asthma is the most prevalent allergic disease of the airway, which is characterized by eosinophilic inflammation, mucus hyperproduction, and airway hyper-responsiveness. Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma. IL-22, one of the cytokines produced by Th17 cells and type 3 ILCs, has distinct functional properties, as IL-22 exclusively acts on non-hematopoietic cells including epithelial cells of mucosal surface and exhibits a broad range of action in regeneration and host protection. In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation. In this review, we discuss recent advances in the biology of IL-22 and its involvement in the pathogenesis of allergic airway inflammation.

https://ift.tt/2qEjCNN

Prognostic models in primary biliary cholangitis

Publication date: Available online 9 November 2018

Source: Journal of Autoimmunity

Author(s): Laura Cristoferi, Alessandra Nardi, Vincenzo Ronca, Pietro Invernizzi, George Mells, Marco Carbone

Abstract

Risk prediction modelling is important to better understand the determinants of the course and outcome of PBC and to inform the risk across the disease continuum in PBC enabling risk-stratified follow-up care and personalised therapy. Current prognostic models in PBC are based on treatment response to ursodeoxycholic acid because of the well-established relationship between alkaline phosphatase on treatment and long-term outcome. In addition, serum alkaline phosphatase correlates with ductular reaction and biliary metaplasia, which are hallmark of biliary injury. Considering the waiting time for treatment failure in high-risk patients is not inconsequential, efforts are focused on bringing forward risk stratification at diagnosis by predicting treatment response at onset.

There is a need for better prognostic variables that are central to the disease process. We should take an integrative approach that incorporates multiple layers of information including genetic and environmental influences, host characteristics, clinical data, and molecular alterations for risk assessments. Biomarker discovery has an accelerated pace taking advantage of the emergence of large-scale omics platforms (genomics, epigenomics, transcriptomics, proteomics, metabolomics, and others) and whole-genome sequencing. In the digital era, applications of artificial intelligence, such as machine learning, can support the computing power required to analyse the vast amount of data produced by omics. The information is then used for the development of personalised risk prediction models that through clinical trials and hopefully industry partnerships can guide risk management strategies. We are facing an unprecedented opportunity for the integration of molecular diagnostics into the clinic, which promotes progress toward the personalised management of patients with PBC.

https://ift.tt/2OBYD8a

Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis

Publication date: Available online 9 November 2018

Source: Journal of Autoimmunity

Author(s): Peter Lamprecht, Nicole Fischer, Jiabin Huang, Lia Burkhardt, Marc Lütgehetmann, Fabian Arndt, Ida Rolfs, Anja Kerstein, Christof Iking-Konert, Martin Laudien

Abstract

Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3–V4 region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruses were detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samples to determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiome diversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbial richness were significantly decreased in GPA samples compared with RA samples. The relative abundance of bacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae, Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae, and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasal microbiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed in GPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our study uncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that both immunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiome interactions in the URT could influence chronic endonasal inflammation in GPA.

https://ift.tt/2OC4yd9

Implementing universal newborn hearing screening in the French Rhône-Alpes region. State of affairs in 2016 and the 1st half of 2017

Publication date: Available online 10 November 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Lorène Bouillot, Maurice Vercherat, Catherine Durand

ABSTRACT

Introduction

Universal newborn hearing screening (UNHS) started as public health policy in 2015 in the French Rhône-Alpes region, aiming to screen for unilateral and bilateral hearing loss. After a first and second screening (retest) in the maternity hospital, the diagnostic process occurred at a limited number of specialist centers. A deferred preliminary screening (T3) was proposed before the age of 1 month. The aims of this study were to assess implementation of the program, impact of T3, and present the incidence of hearing loss in this population.

Materials and methods

The retrospective observational study was based on data transmitted routinely by the 51 maternities to the regional organization responsible for newborn screening, in 2016 and first half of 2017.

Results

All the facilities implemented the UNHS protocol, with 47 out of 51 using the recommended techniques. 99.7% of the 115,435 newborns were screened (excluding 0.2% of parental refusals). A retest was required for 10.2% of the babies. Among babies who didn't pass retest, 7.7% were lost to follow-up. 2.2% of the newborns were referred to diagnostic centers. The rate of T3 was 31.3% of newborns who did not pass retest. 88.6% of the infants passed T3. In the perinatal network making extensive use of T3 (75.8 % versus 14.9% elsewhere), 0.6 % of the infants were referred to a diagnostic center, versus 2.9% in the rest of the region (2016, p<0.001). For 2016, the outcomes at 6 months revealed an overall hearing loss rate of 1.7‰ (4.7‰ for neonatal care unit babies), and bilateral hearing loss in 1.2‰.

Conclusion

In Rhône-Alpes, the national and regional objectives for UNHS were exceeded, although limiting the number of infants lost to follow-up remains essential. Repeating an automated test around 2-4 weeks after birth improves the program by decreasing the false positives of the screening. It considerably limits the number of infants referred to specialist centers, without increasing the number of patients lost to follow-up.

https://ift.tt/2zFQ8TY

A 3-Dimensional Bioprinted Tracheal Segment Implant Pilot Study: Rabbit Tracheal Resection with Graft Implantation

Publication date: Available online 10 November 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Rachel Kaye, Todd Goldstein, Daniel A. Grande, David Zeltsman, Lee P. Smith

Abstract

Objectives

Surgical reconstruction of tracheal disease has expanded to include bioengineering and three dimensional (3D) printing. This pilot study investigates the viability of introducing a living functional tracheal replacement graft in a rabbit animal model.

Methods

Seven New Zealand White rabbits were enrolled and six completed participation (one intraoperative mortality). Tracheal replacement grafts were created by impregnating 3D printed biodegradable polycaprolactone (PCL) tracheal scaffolds with rabbit tracheal hyaline chondrocytes. 2cm of native trachea was resected and the tracheal replacement graft implanted. Subjects were divided into two equal groups (n=3) that differed in their time of harvest following implantation (three or six weeks). Tracheal specimens were analyzed with intraluminal telescopic visualization and histopathology.

Results

The two groups did not significantly differ in histopathology or intraluminal diameter. All sections wherein the implant telescoped over native trachea (anastomotic ends) contained adequate hyaline cartilage formation (i.e. chondrocytes within lacuna, surrounding extracellular matrix, and strong Safranin O staining). Furthermore, the PCL scaffold was surrounded by a thin layer of fibrous tissue. All areas without membranous coverage contained inadequate or immature cartilage formation with inflammation. The average intraluminal stenosis was 83.4% (range 34.2-95%).

Conclusions

We report normal cartilage growth in a tracheal replacement graft when chondrocytes are separated from the tracheal lumen by an intervening membrane. When no such membrane exists there is a propensity for inflammation and stenosis. These findings are important for future construction and implantation of tracheal replacement grafts.

https://ift.tt/2T7uEZh

Beals Syndrome with Middle and Inner Ear Dysplasia and Encephalocele: A Case Report and Review of Imaging Findings

Publication date: Available online 10 November 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Elizabeth K. Weidman, Peter F. Morgenstern, C. Douglas Phillips, Jeffrey P. Greenfield, Theodore H. Schwartz, Linda A. Heier

Abstract

A 10-year-old male with history of Beals syndrome presented with hearing loss and was found to have middle and inner ear dysplasia and left temporal encephalocele on imaging. Beals syndrome is a rare autosomal dominant connective tissue disorder caused by a mutation in the fibrillin-2 gene. Skeletal manifestations of Beals have been reported, including anomalies of the long bones, calvarium, and spine. External ear abnormalities with "crumpled ear" deformity are seen in the majority of patients. This is the first case to report imaging findings of the middle and inner ear in a patient with Beals.

https://ift.tt/2zLWvF8

New insights into immune cells cross-talk during IgG4-related disease

Publication date: Available online 10 November 2018

Source: Clinical Immunology

Author(s): Fahd Touzani, Agnieszka Pozdzik

Abstract

Immunoglobulin G4-related disease (IgG4-RD) is a newly acknowledged entity, characterized by an immune-mediated fibro-inflammatory process affecting virtually all organs, with infiltration of IgG4⁺ bearing plasma cells. Until today the pathogenesis of IgG4-RD remains unknown. Treatment with anti-CD20 monoclonal antibodies efficiently induced remission and attenuated the secretory phenotype of myofibroblasts responsible of uncontrolled collagen deposition. This supports the pathogenic role of the adaptive immunity, particularly B cell compartment and B cell/T cell interaction. Latest studies have also highlighted the importance of innate immune system that has been underestimated before and the key role of a specific T cell subset, T follicular helper cells that are involved in IgG4-class-switching and plasmablast differentiation. In this review, we aim to review the most recent knowledge of innate immunity, T and B cells involvement in IgG4-RD, and introduce tertiary lymphoid organs (TLO) as a potential marker of relapse in this condition.

https://ift.tt/2FpujhM

Neurophysiology of spontaneous facial expressions: II. Motor control of the right and left face is partially independent in adults

Publication date: Available online 10 November 2018

Source: Cortex

Author(s): Elliott D. Ross, Smita S. Gupta, Asif M. Adnan, Thomas L. Holden, Joseph Havlicek, Sridhar Radhakrishnan

Abstract

Facial expressions are described traditionally as monolithic or unitary entities. However, humans have the capacity to produce facial blends of emotion in which the upper and lower face simultaneously display different expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face in each hemisphere that, presumably, also occur in humans. Using high-speed videography, we began measuring the movement dynamics of spontaneous facial expressions, including facial blends, to develop a more complete understanding of the neurophysiology underlying facial expressions. In our part 1 publication in Cortex (2016), we found that hemispheric motor control of the upper and lower face is overwhelmingly independent; 242 (99%) of the expressions were classified as demonstrating independent hemispheric motor control whereas only 3 (1%) were classified as demonstrating dependent hemispheric motor control. In this companion paper (part 2), 251 unitary facial expressions that occurred on either the upper or lower face were analyzed. 164 (65%) expressions demonstrated dependent hemispheric motor control whereas 87 (35%) expressions demonstrated independent or dual hemispheric motor control, indicating that some expressions represent facial blends of emotion that occur across the vertical facial axis. These findings also support the concepts that 1) spontaneous facial expressions are organized predominantly across the horizontal facial axis and secondarily across the vertical facial axis and 2) facial expressions are complex, multi-component, motoric events. Based on the Emotion-type hypothesis of cerebral lateralization, we propose that facial expressions modulated by a primary-emotional response to an environmental event are initiated by the right hemisphere on the left side of the face whereas facial expressions modulated by a social-emotional response to an environmental event are initiated by the left hemisphere on the right side of the face.

https://ift.tt/2OAMGPV

Pattern classification differentiates decision of intertemporal choices using multi-voxel pattern analysis

Publication date: Available online 10 November 2018

Source: Cortex

Author(s): Zhiyi Chen, Yiqun Guo, Shunmin Zhang, Tingyong Feng

Abstract

In daily life, individuals frequently make trade-offs between the small-but-immediate benefits and large-but-delayed profits. This type of decision is known as intertemporal choice. Previous studies have uncovered the neurobiological mechanism of the intertemporal choice, but it still remains unclear how the patterns of brain activity predict the decisions of intertemporal choices. To fill this gap, we used functional magnetic resonance imaging (fMRI), in conjunction with the machine learning technique of multi-voxel pattern analysis (MVPA), to ascertain the predictive capability of the neuronal pattern for classifying individuals' intertemporal decisions across two independent samples. To further probe how this neuronal pattern worked in predicting individual intertemporal decision, we drew on the Power Atlas to examine the accuracies of classification within each regional mask as well. Classification findings showed that the pattern of neuronal activity over the whole-brain can correctly classify the accuracies of individual decisions up to 84.3 %. Encouragingly, further analysis shows that the neuronal information encoded in three brain functional networks can predict individuals' decisions with significant discriminative power in cross-samples, namely the valuation network (e.g., striatum), the cognitive control network (e.g., dorsolateral prefrontal cortex) and the episodic prospection network (e.g., amygdala, parahippocampus gyrus, insula). Collectively, these findings advance our comprehension of the neuronal mechanism of human intertemporal decisions, and substantially reshape our understanding for this cardinal behaviour from behavioural-brain scheme to brain-behavioural configuration.

https://ift.tt/2z1iR5Z

Mapping GABA and Glutamate inputs to gonadotropin‐releasing hormone (GnRH) neurones in male and female mice

Abstract

Gonadotropin releasing hormone (GnRH) neurone function is dependent upon gonadal steroid hormone feedback, which is communicated in large part through an afferent neuronal network. The classical neurotransmitters gamma‐aminobutyric acid (GABA) and glutamate are important regulators of GnRH neurone activity and are implicated in mediating feedback signals. We aimed here to determine whether GABAergic or glutamatergic input to GnRH neurones differs between males and females and/or exhibits morphological plasticity in response to steroid hormone feedback in females. Tissue collected from GnRH‐green fluorescent protein (GFP) male and female mice in diestrus underwent immunofluorescent labelling of GFP and either the vesicular GABA transporter (VGAT) or the vesicular glutamate transporter 2 (VGLUT2). No differences in the densities or absolute numbers of VGAT‐immunoreactive (‐ir) or VGLUT2‐ir puncta apposed to GnRH neurones were identified between males and females. The most significant input from either neurotransmitter was to the proximal dendritic region, and 80% of VGAT‐ir puncta apposed to GnRH neurones co‐localised with synaptophysin. Putative inputs were also assessed in ovariectomised (OVX) female mice treated with negative (OVX+E) or positive (OVX+E+E) feedback levels of oestrogen, and OVX+E+E mice were killed during the expected GnRH/luteinising hormone surge. No differences in VGLUT2‐ir contacts to GnRH neurones were identified between animals under the negative feedback influence of oestrogen (OVX+E) or the positive influence of oestrogen (OVX+E+E), regardless of cFos activation status. In contrast, a significant elevation in putative GABAergic inputs to GnRH neurones at the time of the preovulatory surge was found in the cFos‐negative subset of GnRH neurones, both at the level of the soma and at the proximal dendrite. Together, these data suggest that although GABAergic and glutamatergic innervation of GnRH neurones is not sexually differentiated, cyclic fluctuations in steroid hormone feedback over the female estrous cycle results in plastic changes in GABAergic inputs to a subpopulation of GnRH neurones.

This article is protected by copyright. All rights reserved.

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Interplay of central and peripheral circadian clocks in energy metabolism regulation

Abstract

Metabolic health founds on a homeostatic balance which has to integrate the daily changes of rest/activity and feeding/fasting cycles. A network of endogenous 24‐hour circadian clocks helps to anticipate daily recurring events and adjust physiology and behavioral functions accordingly. Circadian clocks are self‐sustained cellular oscillators based on a set of clock genes/proteins organized in interlocked transcriptional‐translational feedback loops. The body's clocks need to be regularly reset and synchronized with each other to achieve coherent rhythmic output signals. This synchronization is achieved by interplay of a master clock, which resides in the suprachiasmatic nucleus (SCN), and peripheral tissue clocks. This clock network is reset by time signals like the light/dark cycle, food intake, and activity. The balanced interplay of clocks is easily disturbed in modern society by shiftwork or high‐calorie diets which may further promote the development of metabolic disorders. In this review, we summarize the current model of central‐peripheral clock interaction in metabolic health. Different established mouse models for central or peripheral clock disruption and their metabolic phenotypes are compared and the possible relevance of clock network interaction for the development of therapeutic approaches in humans discussed.

This article is protected by copyright. All rights reserved.

https://ift.tt/2JUQquV

Degenerated Hair Follicle Cells and Partial Loss of Sebaceous and Eccrine Glands in a Familial Case of Axenfeld-Rieger Syndrome: An Emerging Role for the FOXC1/NFATC1 Genetic Axis

Publication date: Available online 10 November 2018

Source: Journal of Dermatological Science

Author(s): Hadla Hariri, Mazen Kurban, Christiane Al-Haddad, Akl C. Fahed, Sarin Poladian, Athar Kahlil, Oussama Abbas, Mariam Arabi, Fadi Bitar, Georges Nemer

Abstract

Background

Cutaneous malformations are at times associated with some forms of congenital heart defects. Many a times subtle cutaneous phenotypes maybe overlooked as their significance on the lives of individuals is minimal. Lebanon represents an area of high consanguinity, where the rates can go beyond 70% in some districts. For the past 6 years, we have been studying several genodermatoses in Lebanon including those with cardiac malformations.

Objectives

The main aim of this study is to document the genetic basis of a familial case of Axenfeld-Rieger Syndrome (ARS) with a mild cutaneous phenotype represented histologically with degeneration/ absence of hair follicles and incomplete formation of sebaceous and eccrine glands, in addition to the cardiac and ocular phenotypes.

Methods

Whole exome sequencing was performed on two identical-twins with ARS along with their affected father and non-affected mother. Sanger sequencing was used to confirm the mutation, and the effects of the mutations on protein function was assessed in vitro using transient transfections.

Results

A novel mutation inFOXC1 designated p.L240Rfs*75 was found in both twins and their father. The affected individuals share also a rare documented variant in NFATC1 designated p.V197 M. Both were absent from 200 Lebanese exomes. Our in vitro results suggested a gain of function activity of the FOXC1/NFATC1 complex, confirming its documented role in controlling murine hair follicle stem cells quiescence and regeneration.

Conclusion

This is the first documented human case with a mutation inFOXC1 regulating multi-organ developmental pathways that reflect a conserved mechanism in cell differentiation and proliferation.

https://ift.tt/2QASWZU

A comparison of the 7th and 8th editions of the AJCC staging system in terms of predicting recurrence and survival in patients with papillary thyroid carcinoma

Publication date: December 2018

Source: Oral Oncology, Volume 87

Author(s): Sung Hoon Nam, Mi Rye Bae, Jong-Lyel Roh, Gyungyup Gong, Kyung-Ja Cho, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim

Abstract

Objectives

The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC).

Methods

This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables.

Results

A significant number of patients classified as T3 with overall TNM stages II–IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P < 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P < 0.05), with better predictability of recurrence and survival, in patients with PTC.

Conclusions

The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system.

Condensed abstract

This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system.

https://ift.tt/2Fh1iog

Potential application of tumor suppressor microRNAs for targeted therapy in head and neck cancer: A mini-review

Publication date: December 2018

Source: Oral Oncology, Volume 87

Author(s): Isaac Olatunji

Abstract

Head and neck cancer remains a leading cause of death worldwide. Most common available treatment methods which include surgery, radiotherapy, and chemotherapy are associated with numerous side effects. MicroRNA therapeutics is an emerging form of gene therapy with potential for use in treatment of head and neck cancer. MicroRNAs are short nucleotide RNAs that target mRNAs (messenger RNA) to regulate gene expression at the post-transcription level. They may act as either tumor suppressor or oncogene in cancer. In the past, their potential use in cancer management (diagnosis, treatment, prognosis prediction), based on their deregulation have been demonstrated and written about but summaries on their application for targeted therapy are limited. This article aims at discussing the potential of some known tumor suppressor microRNAs for treatment of head and neck cancer, either alone or in combination with other treatment forms. It also aims at highlighting some obstacles against their use. The search for literature was done on PubMed using the search term: "MicroRNA based head and neck cancer treatment". Only free full text original articles on specific microRNAs and their tumor suppressive abilities in head and neck cancer, written in English language were used. Most of the studies demonstrated the ability of microRNAs to inhibit tumor growth by targeting specific oncogenes in cancer cells. Tumor suppressor microRNAs show promise for the treatment of head and neck cancer but more researches are needed to further clear areas of concern.

https://ift.tt/2qBp58i

Is the World Health Organization predicted exposure assessment model for space spraying of insecticides applicable to agricultural farmers?

Abstract

Agricultural farmers in developing countries are at high risk of pesticide exposure and adverse effects because of unsafe practices and inappropriate legislation. Biological monitoring is considered a useful tool for pesticide exposure assessment; however, its use is limited in developing countries due to a lack of techniques and resources such as laboratory analysis, trained staff and budgets. This study examines whether the World Health Organization predicted exposure assessment model (WHO-PEAM) is a suitable alternative tool for assessing insecticide exposure among agricultural farmers. WHO-PEAM was used to predict daily doses (PDD) of chlorpyrifos for a group of Vietnamese rice farmers using a set of exposure parameters obtained from a questionnaire survey of participant famers during a field study. These results were compared to absorbed daily doses (ADD) of chlorpyrifos for the farmers measured using a biological monitoring program, in which 24-h urine samples were collected and analysed for the chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCP) using LC/MS. Validation of the model results was tested using the Wilcoxon signed-rank test (WSR) and two-way mixed-model intraclass correlation coefficient (ICC). The mean of total ADD was 20 μg/kg/day while that of total PDD was 22 μg/kg/day. The WSR test revealed no statistically significant difference in the average values of ADD_T and PDD_T. ICC indicated substantial agreement for both single and average measures between ADD_T and PDD_T (ICC, 0.62 and 0.77, respectively). The results demonstrate that a refined WHO-PEAM model can be readily used as a field method, without biological monitoring, to evaluate chlorpyrifos exposure among agricultural farmers in Vietnam and similar developing countries.

https://ift.tt/2DAUuA0